Action Points

Note that IL-6 weakly correlated with radiographic progression, but other biomarkers found in prior studies to be significantly associated with AS imaging changes were not confirmed.

An extensive serum biomarker analysis in patients with ankylosing spondylitis (AS) who were treated with golimumab (Simponi) found few biomarkers that correlated with disease activity or changes in magnetic resonance imaging (MRI) findings. Only a weak correlation between interleukin (IL)-6 level and radiographic progression of disease was found.

"The search for serum biomarkers of prognostic utility in AS reflects, in part, the need for objective measures of disease activity and response to treatment, as well as the unresolved issues of pathogenesis in the disease," wrote the study's authors, led by Robert D. Inman, MD, from the University of Toronto, Canada.

The analysis is a sub-study of the large multinational placebo-controlled phase 3 GO-RAISE study of golimumab in patients with AS. As the authors reported in Arthritis Research & Therapy, significant and moderately strong correlations were observed between the AS Disease Activity Score (ASDAS) and levels of IL-6, intracellular adhesion molecule (ICAM)-1, haptoglobin, serum amyloid-P, and C3. "As expected, similar results were observed for C-reactive protein (CRP)," they wrote. "These correlations suggest possible roles for these biomarkers in AS-related inflammation."

In GO-RAISE, 356 patients with AS were randomized to placebo (n=78) or subcutaneous golimumab, 50 mg or 100 mg (n=278), every 4 weeks through week 24. Patients who continued in the study received open-label golimumab through week 252.

Serum samples were collected for biomarker analysis in up to 139 patients, and up to 125 patients underwent serial spine MRI scans (sagittal plane, 1.5-T scanner). Two blinded readers employed the modified AS spine MRI score for activity (ASspiMRI-a) and the AS spine MRI score for chronicity.

At baseline, among the 98 to 139 patients with serum biomarker assessments, significant and moderately strong correlations were observed between ASDAS and levels of IL-6, ICAM-1, haptoglobin, serum amyloid-P and C3 (rs=0.39-0.59, all P≤0.01). The ASDAS also correlated with CRP (rs=0.66, P=0.00).

There were no significant correlations between baseline serum markers and baseline spinal inflammation (ASspiMRI-a score) or structural lesions (ASspiMRI-c score).

Using a generalized linear model, only baseline serum IL-6 levels were found to significantly predict change in the modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) at week 104 (β=0.236, P=0.002).

Logistic regression analyses revealed that baseline levels of leptin, C3, and TIMP-1 were significant predictors for the development of new fatty lesions in the spine at both week 14 and week 104 of golimumab treatment. The change from baseline to week 14 in TIMP-1 was also a significant factor in the development of fatty lesions at week 104.

"Whereas most of these predictive relationships were very weak, those between higher baseline C3 levels and the seven-to eight-fold lower risk of subsequent fatty lesion development were of note," Inman and co-investigators wrote. This finding suggests that leptin and C3 are key regulators of local adipogenesis within bone tissue in AS, they added.

Significant correlates of improvement in ASspiMRI-a scores from baseline to week 14 of golimumab treatment were improvement from baseline to week 4 in serum IL-6 (rs=0.61, P=0.022) and C3 (rs=0.72, P=0.005), and improvement from baseline to week 14 in serum IL-6 levels (rs=0.59, P=0.043).

Among limitations, the authors identified the crossover to active therapy after a short placebo period, the few patients on which to base correlation analyses for radiographic progression and development of fatty lesions, and the lack of adjustment for potential confounders in assessing relationships between IL-6 and MRI-detected spinal inflammation and clinical measures of disease activity.

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